The main physiological function of lipoxygenases is the formation of mediators in inflammation and cellular differentiation. Most prominently, 5-lipoxygenase and its leukotriene products are involved in bronchoconstriction and inflammation. A subgroup of epithelial lipoxygenases is suggested to play a role in the regulation or modulation of normal proliferation and differentiation of epithelial cells. For example, psoriasis and other proliferative skin diseases are associated with impaired function of epidermal lipoxygenases. Human eLOX3 is the most recent membr of the subfamily of epithelial lipoxygenases, and it is unique for two reasons: eLOX3 does not catalyze the normal lipoxygenase reaction, yet it does metabolize lipoxygenase products to skin-specific epoxy alcohols. Secondly, exon 1 of the human eLOX3 mRNA is unique among all lipoxygenases in that it has two functional translation initiation sites giving rise either to a cytosolic or to a nuclear form of the protein. The overall goal of this proposal is to provide initial insight into how the physiological role of eLOX3 is determined by its differential subcellular localization. I propose experiments that will establish the tissue distribution of the cytosolic and nuclear eLOX3, and provide insight into the regulation of eLOX3 expression and subcellular localization. To better understand the functional role of eLOX3 expression in the nucleus interacting proteins will be identified using a yeast two hybrid screening assay and co-immunoprecipitations. Finally, cultured keratinocytes will be used to investigate nuclear expression of eLOX3 during differentiation.